BMS-986489 + Nivolumab vs Durvalumab for Small Cell Lung Cancer

(TIGOS-LS Trial)

Recruiting at 27 trial locations

Overseen By Sarah Cannon Development Innovations, LLC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: SCRI Development Innovations, LLC

Must be taking: Platinum, Etoposide

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Heart conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for small cell lung cancer (SCLC) that hasn't spread widely. The main goal is to compare the effectiveness of a new treatment, BMS-986489 (an experimental combination of atigotatug and nivolumab), with durvalumab, an existing treatment. Researchers also aim to assess the safety of the new treatment. This trial suits individuals who have completed chemotherapy and radiation for limited-stage SCLC without disease progression. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not be on chronic immunosuppressive medications or systemic corticosteroids above a certain dose. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that BMS-986489, when used with nivolumab, has not yet received FDA approval for safety or effectiveness in treating extensive-stage small cell lung cancer (SCLC). Current studies have not clearly demonstrated its safety. Since this treatment is in a Phase 2 trial, some early safety checks have been completed, but more information is needed to fully understand its safety in people.

In contrast, durvalumab, which is being compared in the study, is an approved treatment for some cancers. Its safety profile is well-known, meaning researchers understand its side effects and how patients handle it.

Prospective trial participants should know that while durvalumab has established safety data, BMS-986489 with nivolumab is still under investigation for safety. Participants might experience unknown side effects with the experimental combination. Consulting a healthcare provider is crucial to consider these factors and understand the implications of joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for small cell lung cancer?

Researchers are excited about BMS-986489 (atigotatug + nivolumab) because it combines two powerful agents that work together to tackle small cell lung cancer differently. Unlike the standard treatments like chemotherapy or single-agent immunotherapies, this combination leverages nivolumab, an immune checkpoint inhibitor, with atigotatug, potentially enhancing the immune system's ability to recognize and destroy cancer cells more effectively. This dual action could lead to better outcomes by not only slowing tumor growth but also boosting the overall immune response against the cancer.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

This trial will compare the combination of BMS-986489 (atigotatug) and nivolumab with Durvalumab for treating limited-stage small-cell lung cancer (SCLC). Research has shown that the combination of BMS-986489 and nivolumab may help treat SCLC. In one study, patients who received this combination lived for a median of 11.6 months and had a median time of 2.9 months during which their cancer did not worsen. These findings suggest that this treatment could be beneficial in managing SCLC. Additionally, previous studies have found nivolumab, part of this combination, to be more effective than some standard treatments. This evidence supports the potential effectiveness of BMS-986489 plus nivolumab in treating SCLC. Meanwhile, Durvalumab, which participants in another arm of this trial will receive, is a standard treatment option for SCLC. ^{1 2 6 7 8}

Who Is on the Research Team?

Melissa Johnson, MD

Principal Investigator

SCRI Development Innovations, LLC

Are You a Good Fit for This Trial?

This trial is for adults with small-cell lung cancer who've finished chemo and radiotherapy without the disease getting worse. They must have good blood and organ function, be willing to use birth control, and have a performance status showing they're mostly active.

Inclusion Criteria

I agree to follow the study's birth control rules.

I may have brain radiation to prevent cancer spread, done 14-42 days before starting the study treatment.

I am fully active or restricted in physically strenuous activity but can do light work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiotherapy

Participants receive concurrent chemotherapy and radiotherapy according to standard guidelines for treatment of LS-SCLC

6-8 weeks

Consolidation Therapy

Participants receive either BMS-986489 (atigotatug + nivolumab) or durvalumab as consolidation therapy

Up to 3 years

Every 2 cycles (8 weeks) for the first 6 months, then every 3 cycles (12 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 8 weeks for participants who stopped treatment before disease progression and before completing 6 months of treatment and every 12 weeks for participants who stopped treatment before disease progression

What Are the Treatments Tested in This Trial?

Interventions

• BMS-986489
• Durvalumab

Trial Overview

The study compares BMS-986489 (a combination of atigotatug + nivolumab) with durvalumab in patients with limited-stage small-cell lung cancer. It's an open-label trial, meaning everyone knows which treatment they receive.

How Is the Trial Designed?

Group I: BMS-986489 (atigotatug + nivolumab) Experimental Treatment 1 Intervention

Participants will receive a fixed dose of BMS-986489 (atigotatug + nivolumab) intravenously each cycle. Cycles will be 28 days. Up to 125 participants will be enrolled into this arm.

Group II: Durvalumab Active Control 1 Intervention

Participants will receive standard of care Durvalumab intravenously each cycle. Cycles will be 28 days. Up to 125 participants will be enrolled into this arm.

Who Is Running the Clinical Trial?

SCRI Development Innovations, LLC

Lead Sponsor

Trials

193

Recruited

13,800+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

In a phase II trial involving 116 patients with squamous non-small-cell lung cancer, durvalumab demonstrated a 16% overall response rate and a disease control rate of 54%, indicating its potential effectiveness as a treatment after platinum-based chemotherapy.

The treatment was associated with a median overall survival of 11.6 months and a median progression-free survival of 2.9 months, with 32% of patients experiencing grade ≥ 3 treatment-related adverse events, suggesting that while durvalumab is active, it also carries a risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SWOG S1400A (NCT02154490): A Phase II Study of Durvalumab for Patients With Previously Treated Stage IV or Recurrent Squamous Cell Lung Cancer (Lung-MAP Sub-study). Borghaei, H., Redman, MW., Kelly, K., et al.[2022]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

In the phase II ATLANTIC study, durvalumab demonstrated encouraging overall survival (OS) rates in heavily pretreated patients with advanced non-small cell lung cancer (NSCLC), with median OS ranging from 9.3 to 13.3 months depending on tumor characteristics.

The safety profile of durvalumab remained consistent with previous reports, showing no new safety concerns, indicating it is a tolerable treatment option for patients with advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final overall survival and safety update for durvalumab in third- or later-line advanced NSCLC: The phase II ATLANTIC study. Garassino, MC., Cho, BC., Kim, JH., et al.[2021]

In a study of 421 patients with stage III nonsmall-cell lung cancer (NSCLC) who completed chemoradiation, 76.5% initiated adjuvant durvalumab, indicating a strong uptake of this treatment in real-world settings.

The initiation of adjuvant durvalumab increased significantly over time, from 66% to 92%, suggesting that it has been rapidly integrated into clinical practice, particularly among patients with better performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uptake of Adjuvant Durvalumab After Definitive Concurrent Chemoradiotherapy for Stage III Nonsmall-cell Lung Cancer. Bryant, AK., Yin, H., Schipper, MJ., et al.[2023]

Durvalumab, an immune checkpoint inhibitor, has shown promising efficacy in treating advanced non-small cell lung cancer (NSCLC) in early phase trials, demonstrating a good safety profile.

The PACIFIC trial has successfully met its primary endpoint, indicating that durvalumab may be an important part of future treatment strategies for NSCLC, with ongoing studies potentially confirming its superiority over current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI 4736 (durvalumab) in non-small cell lung cancer. Jeanson, A., Barlesi, F.[2021]

In a phase 2 trial involving 444 patients with advanced non-small-cell lung cancer (NSCLC), durvalumab (an anti-PD-L1 treatment) showed a response rate of 30.9% in patients with ≥90% PD-L1 expression, indicating its potential efficacy in heavily pretreated cases.

The safety profile of durvalumab was consistent with other similar treatments, with 9% of patients experiencing grade 3 or 4 treatment-related adverse events, suggesting it is manageable and generally safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Garassino, MC., Cho, BC., Kim, JH., et al.[2022]

In the CASPIAN trial, first-line treatment with durvalumab plus platinum-etoposide significantly improved overall survival in patients with extensive-stage small cell lung cancer, showing consistent benefits regardless of PD-L1 expression or tissue tumor mutational burden status.

The study found that while PD-L1 expression may be a useful biomarker for treatment response, the overall survival benefit of durvalumab plus EP was similar across different PD-L1 subgroups, indicating that this treatment could be effective for a broad range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab ± tremelimumab + platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): outcomes by PD-L1 expression and tissue tumor mutational burden. Paz-Ares, L., Garassino, MC., Chen, Y., et al.[2023]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06773910

NCT06773910 | BMS-986489 (Atigotatug + Nivolumab) vs ...

This is an open-label, randomized study of BMS-986489 (atigotatug + nivolumab fixed-dose combination) vs durvalumab in limited-stage (LS)-small-cell lung ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS8127

The TIGOS trial: A randomized, double-blind phase 3 ...

A randomized, double-blind, multicenter phase 3 trial to compare the efficacy and safety of atigotatug + nivolumab fixed-dose combination with chemotherapy vs ...

3.

withpower.com

withpower.com/trial/phase-2-small-cell-lung-carcinoma-2-2025-c4088

BMS-986489 + Nivolumab vs Durvalumab for Small Cell ...

The treatment was associated with a median overall survival of 11.6 months and a median progression-free survival of 2.9 months, with 32% of patients ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/33140652/

Comparative effectiveness of nivolumab versus standard ...

Nivolumab was more efficacious in terms of OS as third-line treatment for small-cell lung cancer compared with current SOC in the USA.

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0923753421000995

Second-line nivolumab in relapsed small-cell lung cancer

Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline ...

6.

bmsclinicaltrials.com

bmsclinicaltrials.com/us/en/tigos-hcp/how-tigos-work

How BMS-986489 Works in SCLC

BMS-986489 is not currently approved in any market and has not been approved by the FDA as safe or effective for Extensive-Stage Small Cell Lung Cancer.

7.

clinicaltrial.be

clinicaltrial.be/en/details/455090?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

A Study to Compare the Efficacy and Safety of BMS-986489...

The Purpose of the Study is to Compare the Efficacy and Safety of BMS-986489 (Anti-fucosyl-GM1+ Nivolumab Fixed Dose Combination) in Combination with ...

8.

news.bms.com

news.bms.com/news/details/2025/Bristol-Myers-Squibb-Announces-Opdivo-Plus-Chemotherapy-as-the-First-and-Only-Neoadjuvant-Only-Immuno-Oncology-Therapy-to-Demonstrate-Statistically-Significant-and-Clinically-Meaningful-Overall-Survival-in-Resectable-Non-Small-Cell-Lung-Cancer/default.aspx

The final analysis of overall survival in the CheckMate

Bristol Myers Squibb (NYSE: BMY) today announced the final analysis of overall survival (OS) from the Phase 3 CheckMate -816 study, ...